Synthesis of new 3-phenoxypropan-2-ols with various heterocyclic substituents

Article abstract of DOI:10.1007/s11178-005-0122-1

1-Phenoxy-3-piperidinopropan-2-ol, 1-(5-methyl-1,3-benzothiazol-2- ylsulfanyl)-3-phenoxypropan-2-ol, 1-(2-hydroxy-3-phenoxypropyl)azepan-2-one, 1,1′-(6-chloro-1,3-benzothiazol-2-ylimino)bis(3-phenoxypropan-2-ol), 1-(1,3-benzothiazol-2-ylsulfanyl)-3-phenox

Full text of DOI:10.1007/s11178-005-0122-1

Russian Journal of Organic Chemistry, Vol. 41, No. 1, 2005, pp. 67 -69. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005,
pp. 70-72.
Original Russian Text Copyright Ó 2005 by Mesropyan, Ambartsumyan, Avetisyan, Galstyan, Arutyunova.
Synthesis of New 3-Phenoxypropan-2-ols with Various
Heterocyclic Substituents
E. G. Mesropyan, G. B.Ambartsumyan, A.A. Avetisyan,
A. S. Galstyan, and I. R.Arutyunova
Erevan State University, ul. A. Manukyana 1, Erevan, 375049 Armenia
e-mail: mag_union@yahoo.com
Received October 10, 2003
Abstract—1-Phenoxy-3-piperidinopropan-2-ol, 1-(5-methyl-1,3-benzothiazol-2-ylsulfanyl)-3-phenoxypropan-2-ol,
1-(2-hydroxy-3-phenoxypropyl)azepan-2-one, 1,1'-(6-chloro-1,3-benzothiazol-2-ylimino)bis(3-phenoxypropan-2-ol),
1-(1,3-benzothiazol-2-ylsulfanyl)-3-phenoxypropan-2-ol, 1,1'-(piperazine-1,4-diyl)bis(3-phenoxypropan-2-ol), and
1,3-bis(2-hydroxy-3-phenoxypropyl)barbituric acid were synthesized by condensation of 1,2-epoxy-3-
phenoxypropane with the corresponding amines and thiols.
Condensation of 1,2-epoxy-3-phenoxypropane with
piperidine, 5-methyl-1,3-benzothiazole-2-thiol, capro-
lactam, 6-chloro-1,3-benzothiazol-2-amine, 1,3-benzo-
thiazole-2-thiol, piperazine, and barbituric acid afforded
the corresponding 3-substituted 2-hydroxypropyl phenyl
ethers I–VII (Table 1). Systems containing the above
heterocyclic fragments, which are widely known pharma-
cophoric groups, attract interest from the viewpoint of
their biological activity [1–3]. The effects of tempera-
ture, solvent nature, reaction time, and reactant ratio on
the process were examined, and optimal conditions were
found. It should be noted that opening of the oxirane ring
in 1,2-epoxy-3-phenoxypropane occurs according to the
Krasuskii rule, i.e., the hydroxy group appears at the least
hydrogenized carbon atom. This reaction direction is also
favored by steric factor, in keeping with our previous data
[4, 5].
EXPERIMENTAL
1
The H NMR spectra were recorded at 30°C on
a Varian Mercury-300 spectrometer (300 MHz) using
DMSO-d as solvent (Table 2). The IR spectra of
6
compounds I, II, and V–VII were measured on a Specord
75IR spectrophotometer from samples dispersed in
mineral oil. The purity of the products was checked by
TLC on Silufol UV-254 plates; development with iodine
vapor.
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1070-4280/05/4101-0067Ó2005 Pleiades Publishing, Inc.

68
MESROPYAN et al.
Table 1. Yields, boiling or melting points, and elemental analyses of 3-phenoxypropan-2-ols I–VII
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1
-Phenoxy-3-piperidinopropan-2-ol (1). A mixture
of 6 g (0.04 mol) of 1,2-epoxy-3-phenoxypropane and
1.84 g (0.12 mol) of piperidine was heated for 6 h at
20–125°C. Excess piperidine was removed, and the
of 5-methyl-1,3-benzothiazole-2-thiol and 3 g (0.02 mol)
of 1,2-epoxy-3-phenoxypropane was heated for 7 h at
120–125°C. The product was washed with benzene.
Compound II is readily soluble in ethanol, chloroform,
DMF, and DMSO and insoluble in benzene, heptane,
water, and dioxane.
1
1
residue was washed with hexane and recrystallized from
hexane. The product is readily soluble in ethanol,
chloroform, acetone, and DMSO and insoluble in heptane,
water, and dioxane.
1
-(2-Hydroxy-3-phenoxypropyl)azepan-2-one
(
III). A mixture of 6 g (0.04 mol) of 1,2-epoxy-3-
1
-(5-Methyl-1,3-benzothiazol-2-ylsulfanyl)-3-
phenoxypropane, 9.04 g (0.08 mol) of caprolactam, and
0.1 ml of water was heated for 8 h at 120–125°C and
phenoxypropan-2-ol (II). Amixture of 3.6 g (0.02 mol)
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 1 2005

SYNTHESIS OF NEW 3-PHENOXYPROPAN-2-OLS
69
was then distilled under reduced pressure. Compound
III is readily soluble in hot water, diethyl ether, ethanol,
DMF, and DMSO and insoluble in hexane and cold water.
for 4 h at 94–97°C. The precipitate was separated and
washed with ethanol. The product is readily soluble in
hot ethanol, chloroform, and DMSO, and insoluble in cold
ethanol, water, heptane, hexane, and diethyl ether.
1
,1'-(6-Chloro-1,3-benzothiazol-2-ylimino)bis(3-
phenoxypropan-2-ol) (IV). 1,2-Epoxy-3-phenoxy-
propane, 15 g (0.1 mol), was added to a solution of
1
,3-Bis(2-hydroxy-3-phenoxypropyl)barbituric
acid (VII). A mixture of 2.5 g (0.02 mol) of barbituric
acid, 9 g (0.06 mol) of 1,2-epoxy-3-phenoxypropane, and
7
.38 g (0.04 mol) of 6-chloro-1,3-benzothiazol-2-amine
in 20 ml of anhydrous DMF, and the mixture was heated
for 10 h at 95–100°C. The solvent was distilled off, and
the residue was distilled under reduced pressure. Com-
pound IV is readily soluble in chloroform, ethanol, DMF,
and DMSO and insoluble in hexane and water.
3
ml of DMF was heated for 4 h at 94–97°C. The
precipitate was separated and washed with ethanol. The
product is readily soluble in hot ethanol, water, chloroform,
and DMSO and insoluble in cold ethanol, heptane, hexane,
and diethyl ether.
1
-(1,3-Benzothiazol-2-ylsulfanyl)-3-phenoxy-
propan-2-ol (V). 1,2-Epoxy-3-phenoxypropane, 6 g
0.04 mol), was added to a solution of 6.7 g (0.04 mol) of
,3-benzothiazole-2-thiol in 5 ml of anhydrous DMF, and
the mixture was heated for 4 h at 94–97°C. The solvent
was distilled off, and the residue was distilled under
reduced pressure. Compound V is readily soluble in
chloroform, benzene, DMF, DMSO, hot ethanol, and hot
water and insoluble in heptane, cold ethanol, and cold
water.
REFERENCES
(
1
1
. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: Meditsina, 1973, vol. 2, p. 320.
2. Melent’eva, G.A., Farmatsevticheskaya khimiya (Pharma-
ceutical Chemistry), Moscow: Meditsina, 1976, vol. 1, p. 312.
3
. Ushakov, S.N., Bogomolova, L.G., and Davidenkov, V.V.,
Aktual’nye voprosy perelivaniya krovi (Actual Problems
in Blood Transfusion), Moscow: Medgiz, 1954, p. 107.
1
,1'-(Piperazin-1,4-diyl)bis(3-phenoxypropan-2-
4. Mesropyan, E.G.,Ambartsumyan, G.B., andAvetisyan,A.A.,
ol) (VI). 1,2-Epoxy-3-phenoxypropane, 18 g (0.12 mol),
was added to a solution of 5.2 g (0.06 mol) of piperazine
in 5 ml of anhydrous DMF, and the mixture was heated
Russ. J. Org. Chem., 2000, vol. 36, p. 444.
5. Mesropyan, E.G.,Ambartsumyan, G.B., andAvetisyan,A.A.,
Russ. J. Org. Chem., 1998, vol. 34, p. 104.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 1 2005